Device for delivery of oxidizing agents to barrier membranes

ABSTRACT

The present invention features a method of treating infection in a barrier membrane by applying to the membrane a device having a barrier membrane contacting surface that administers an oxidizing agent to the barrier membrane, wherein the device contains: a power source; a first conductive electrode, wherein the first conductive electrode is an inert anode; a second conductive electrode, wherein the second conductive electrode is a cathode; and a carrier containing water; wherein the power source is in electric communication with the first conductive electrode and the second conductive electrode, wherein the first conductive electrode is in ionic communication with the carrier, wherein the oxidizing agent is generated by electric current passing from the first conductive electrode through the carrier, and wherein the carrier is in communication with the barrier membrane contacting surface.

FIELD OF THE INVENTION

The present invention relates to a device for application to a barriermembrane.

BACKGROUND OF THE INVENTION

Transdermal devices have been widely prescribed for decades in thetreatment of is systemic diseases and local conditions. During passivetransdermal delivery, an active agent is delivered into a mammal byusing a concentration gradient across a barrier membrane (e.g., throughpassive diffusion through skin). For example, a patch containing thedrug in high concentration is affixed to the skin of a patient.

Electricity may be employed to facilitate drug transport across the skinbarrier. In electricity-assisted devices, an electric potential(voltage) is applied to the membrane to facilitate drug transport. Intransdermal iontophoresis, an ionized drug migrates into the skin drivenby an applied electric potential gradient. Anionic drugs are deliveredinto the skin under the cathode (negatively charged electrode), whilecationic drugs are delivered under the anode (positively chargedelectrode). Iontophoresis enables enhanced as well as better control ofpermeation rate of the ionic species into the skin.

The most common design of an iontophoresis device includes a powersource (e.g., a battery), an electric control mechanism, and twoseparate conductive electrodes. Each conductive electrode is in contactwith a separate electrolyte composition (with or without an activeagent). The electrolyte or ionic active composition is generally eitheran aqueous solution contained in a liquid chamber or a semi-solid. Theassembly of the conductive electrode and electrolyte composition isoften referred to as “an electrode assembly” or simply “an electrode.”The two electrode assemblies are usually affixed to the skin separatedby electric insulation between them.

Alternatively, the two electrode assemblies may be constructed into asingle iontophoresis device with an electric insulating material builtbetween the two electrode assemblies for electrical isolation to preventshorting current. An example of such an iontophoresis device isdisclosed in U.S. Pat. No. 5,387,189.

In another variation of the common iontophoresis device designs, theelectrolyte composition in one of the two electrode assemblies iseliminated, and the conductive electrode is placed directly in contactwith the skin to complete the electric circuit. An example of suchiontophoresis device is disclosed in U.S. Pat. No. 6,385,487.

During a typical iontophoresis operation (mono-polar operation), one ofthe two electrodes (i.e., active electrode) drives the active agent intothe skin. The other electrode (i.e., disperse electrode) serves to closethe electrical circuit through the skin. Sometimes, a second activeagent of opposite electric charge can be placed into electrolytecomposition in contact with the second electrode, thus, being deliveredinto the skin under the second electrode. Alternatively, the electricpolarity of the first and second electrodes can be reversed periodicallyto drive ionic species under both electrodes (bi-polar operation). Abi-polar iontophoresis device for transdermal drug delivery is disclosedU.S. Pat. No. 4,406,658.

Acne and rosacea are major diseases of the skin associated withsebaceous follicles on the skin. There are many treatments, but no curesfor acne or rosacea. Such treatments for acne include antibiotics (whichkill or inhibit growth of p. acnes bacteria which play a role in acne),retinoids such as tretinoin and isotetinoin, antimicrobials such asbenzoyl peroxide, and keratolytic agents such as salicylic acid. Rosaceacan be treated with antibiotics, sulfur, sodium sulfacetamide, andretinoids. The present invention relates to a device that can be used totreat acne or rosacea, or other conditions that affect barriermembranes.

SUMMARY OF THE INVENTION

In one aspect, the present invention features a device having a barriermembrane contacting surface, the device containing: a power source; afirst conductive electrode; a second conductive electrode; and acarrier; wherein the power source is in electric communication with thefirst conductive electrode and the second conductive electrode, whereinthe first conductive electrode and the second conductive electrode arein ionic communication with the carrier, and wherein the carrier is incommunication with the barrier membrane contacting surface. In anotheraspect, the present invention features a method of administeringelectricity to a human barrier membrane by applying to the membrane sucha device. In another aspect, the present invention features a method oftreating a skin condition by applying to the skin such a device.

In another aspect, the present invention features a device having abarrier membrane contacting surface, the device containing: a powersource; a first conductive electrode; a second conductive electrode; anda carrier containing an active agent; wherein the power source is inelectric communication with the first conductive electrode and thesecond conductive electrode, wherein the first conductive electrode andthe second conductive electrode are in ionic communication with thecarrier, and wherein the carrier is in communication with the barriermembrane contacting surface. In another aspect, the present inventionfeatures a method of administering electricity to a human barriermembrane by applying to the membrane such a device. In another aspect,the present invention features a method of treating a skin condition byapplying to the skin such a device.

In another aspect, the present invention features a device having abarrier membrane contacting surface, the device containing: a powersource; a first conductive electrode; a second conductive electrode; afirst light emitting diode; and a carrier containing an active agent;wherein the power source is in electric communication with the firstconductive electrode, the second conductive electrode, and the lightemitting diode, and wherein the device is arranged such that light fromthe first light emitting diode and the carrier are in communication withthe barrier membrane contacting surface. In another aspect, the presentinvention features a method of administering an active agent to a humanbarrier membrane by applying to the membrane such a device. In anotheraspect, the present invention features a method of treating a skincondition by applying to the skin such a device.

In another aspect, the present invention features a method of treating askin condition by applying to the skin a device having a barriermembrane contacting surface that administers an oxidizing agent to thebarrier membrane, wherein the device contains: a power source; a firstconductive electrode, wherein the first conductive electrode is an inertanode; a second conductive electrode, wherein the second conductiveelectrode is a cathode; and a carrier containing water; wherein thepower source is in electric communication with the first conductiveelectrode and the second conductive electrode, wherein the firstconductive electrode is in ionic communication with the carrier, whereinthe oxidizing agent is generated by electric current passing from thefirst conductive electrode through the carrier, and wherein the carrieris in communication with the barrier membrane contacting surface. Inanother aspect, the present invention features a method of administeringan oxidizing agent to a barrier membrane by applying to the membranesuch a device.

In another aspect, the present invention features a method of treating askin condition by applying to the skin a device having a barriermembrane contacting surface that administers a reducing agent to thebarrier membrane, wherein the device contains: a power source; a firstconductive electrode, wherein the first conductive electrode is an inertcathode; a second conductive electrode, wherein the second conductiveelectrode is a anode; and a carrier containing water; wherein the powersource is in electric communication with the first conductive electrodeand the second conductive electrode, wherein the first conductiveelectrode is in ionic communication with the carrier, wherein thereducing agent is generated by electric current passing from the firstconductive electrode through the carrier, and wherein the carrier is incommunication with the barrier membrane contacting surface. In anotheraspect, the present invention features a method of administering anreducing agent to a barrier membrane by applying to the membrane such adevice.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a cross-sectional view of one embodiment of the devicesuitable for practicing the invention. The battery 320 is located at theback of the device 500.

FIG. 2 is a cross-sectional view of one embodiment in accordance withthe invention. The battery 320 is embedded in the carrier layer 120 ofthe device 500.

FIG. 3 is a cross-sectional view of one embodiment in accordance withthe invention. The battery 320 is embedded in the carrier layer 120 thatis enclosed in a chamber 160 with an opening affixed to the releaseliner 100 with an adhesive layer 130.

FIG. 4 is a top view of one embodiment in accordance with the inventionshowing the conductive electrodes 140 and 240 and carrier layer 120.

FIG. 5 is a top view of one embodiment in accordance with the inventionshowing the conductive electrodes 140 and 240 and carrier layer 120.

FIG. 6 is a cross-sectional view of one embodiment in accordance withthe invention. The device 800 contains two electrode assemblies 200 and600.

DETAILED DESCRIPTION OF THE INVENTION

It is believed that one skilled in the art can, based upon thedescription herein, utilize the present invention to its fullest extent.The following specific embodiments are to be construed as merelyillustrative, and not limitative of the remainder of the disclosure inany way whatsoever.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which the invention belongs. Also, all publications, patentapplications, patents, and other references mentioned herein areincorporated by reference. Unless otherwise indicated, a percentagerefers to a percentage by weight (i.e., % (W/W)).

What is meant by a “product” is a product containing the device infinished packaged form. In one embodiment, the product containsinstructions directing the user to apply the device to the barriermembrane (e.g., to treat a skin condition). Such instructions may beprinted on the device, label insert, or on any additional packaging.

In one aspect, the present invention features promoting a device of thepresent invention for its intended use. What is meant by “promoting” ispromoting, advertising, or marketing. Examples of promoting include, butare not limited to, written, visual, or verbal statements made on theproduct or in stores, magazines, newspaper, radio, television, internet,and the like.

As used herein, “pharmaceutically-acceptable” means that the ingredientswhich the term describes are suitable for use in contact with thebarrier membrane (e.g., the skin or mucosa) without undue toxicity,incompatibility, instability, irritation, allergic response, and thelike.

As used herein, “safe and effective amount” means an amount of theingredient or of the composition sufficient to provide the desiredbenefit at a desired level, but low enough to avoid serious sideeffects. The safe and effective amount of the ingredient or compositionwill vary with the area being treated, the age and skin type of the enduser, the duration and nature of the treatment, the specific ingredientor composition employed, the particular cosmetically-acceptable carrierutilized, and like factors.

As used herein, the term “treatment” means the treatment (e.g.,alleviation or elimination of symptoms and/or cure) and/or prevention orinhibition of the condition (e.g., a skin condition). What is meant by a“skin condition” is a dermatological disease or disorder (including, butnot limited, acne, rosacea, or skin infections) or skin characteristic(including, but not limited to, pigmentation, hair growth regulation,skin texture, skin firmness, skin elasticity, skin vasculature, darkcircles, cellulite, sebum regulation, and skin shine).

The present invention relates to a device for the delivery ofelectricity (e.g., to induce a desirable biological response) and/or anactive agent into a barrier membrane. In one embodiment, the device ofthe present invention is a self-contained device containing a battery aspower source and two conductive electrodes in electric communicationwith the positive and negative poles of the battery. By “electriccommunication” is meant that electrons can pass between the elements ofthe device (e.g., between the power source and an conductive electrodeof the device).

In one embodiment, the two conductive electrodes are in ioniccommunication with the carrier containing an electrolyte. By “ioniccommunication” it meant that ions of one or more electrolytes in thecarrier are in contact with the conductive electrode. This electrodeconfiguration differs from those in conventional iontophoresis devicesin which each conductive electrode is in contact with a separate carrier(e.g., each electrode is contained in a separate compartment and affixedto the skin with electric insulation between them in order that all theelectric current travels through the skin to complete the electriccircuit). An advantage of such an embodiment of the present inventionincludes the capability of delivering simultaneously active agents ofopposite charges from the same carrier into substantially the same skinsite under the conductive electrodes.

The device contains a barrier membrane contacting surface. The device isarranged such that carrier is in communication with the barrier membranecontacting surface (e.g., such that electricity and/or the active agentmay be administered from the carrier into the barrier membrane). In oneembodiment, the carrier is the barrier membrane contacting surface(e.g., the carrier is a hydrogel). In one embodiment, the devicecontains a light emitting diode such that light from the light emittingdiode is in communication with the barrier membrane contacting surface(e.g., such that the light may be administered to the barrier membrane).

In one embodiment, the device of the present invention delivers anactive agent into the barrier membrane. The active agents to bedelivered by the device of the present invention include active agentseither initially incorporated in the carrier or electrochemicallygenerated by the electric current passing from a conductive electrodethrough the carrier during use.

Power Source

The power source may be conventional direct current (DC) or pulsed DC,such as that disclosed in U.S. Pat. No. 5,042,975. In one embodiment,the current density to be used by the device in the present invention(current intensity per unit area of the barrier membrane) is generallyless than about 0.5 mA/cm², such as less than about 0.1 mA/cm² or lessthan about 0.05 mA/cm². In one embodiment, the power source produces avoltage of from about 0.1 volts to about 9 volts, such as from about 1to about 3 volts, such as about 1.5 volts.

In one embodiment, the power source is a battery (e.g., a rechargeableor disposable battery). In one embodiment, the battery is a disposablebattery of small size suitable for a wearable patch or facial mask typeadhesive device. Examples of suitable batteries include, but not limitedto, button or coin batteries such as silver oxide, lithium, and zinc airbatteries (which are typically used in small electronic devices). A zincair battery is preferred because of its small size and high energydensity, as well as its environmental friendliness. Examples of zinc airbatteries include, but are not limited to, Energizer™AC5 and AC10/230(Eveready Battery Co. Inc., St. Louis, Mo.). Another preferred batteryfor the device is a flexible thin layer open liquid stateelectrochemical cell battery, such as a battery described in U.S. Pat.No. 5,897,522.

Carrier

The carrier of the present invention is a liquid (e.g., a solution, asuspension, or an emulsion which may be immobilized within an absorbentmaterial such as gauze or non-woven pad), a semi-solid (e.g., a gel, acream, a lotion, microemulsion, or hydrogel), or a solid (e.g., alyophilized composition which may be reconstituted by adding a liquidprior to use) that during use is capable of conducting electricity froma conducting electrode (e.g., the carrier contains one or moreelectrolytes and water).

Examples of electrolytes include, but are not limited to,pharmaceutically acceptable organic and organic salts and buffers.Examples of salts include, but are not limited to, chloride salts (suchas sodium chloride, potassium chloride, lithium chloride, calciumchloride, strontium chloride, magnesium chloride or other chloridesalts), as well as salts of sodium, potassium, lithium, calcium,magnesium, strontium, fluoride, iodide, bromide. Examples of buffersinclude, but are not limited to, phosphates, citrates, acetates,lactates, and borates In one embodiment, the electrolyte is an activeagent, or becomes an active agent after the passage of the electriccurrent through the carrier. Examples of such electrolyte-active agentsinclude, but are not limited to, salicylic acid, salicylates, and otherweak acid or weak base active agents.

In one embodiment, the carrier contains water. In a further embodiment,the carrier may also contains one or more organic solvents. Examples oforganic solvents include, but are not limited to: dimethyl isosorbide;isopropylmyristate; surfactants of cationic, anionic and nonionicnature; vegetable oils; mineral oils; waxes; gums; synthetic and naturalgelling agents; alkanols; glycols; and polyols.

Examples of glycols include, but are not limited to, glycerin, propyleneglycol, butylene glycol, pentalene glycol, hexylene glycol, polyethyleneglycol, polypropylene glycol, diethylene glycol, triethylene glycol,glycerol, and hexanetriol, and copolymers or mixtures thereof. Examplesof alkanols include, but are not limited to, those having from about 2carbon atoms to about 12 carbon atoms (e.g., from about 2 carbon atomsto about 4 carbon atoms), such as isopropanol and ethanol. Examples ofpolyols include, but are not limited to, those having from about 2carbon atoms to about 15 carbon atoms (e.g., from, about 2 carbon atomsto about 10 carbon atoms) such as propylene glycol.

The organic solvents may be present in the carrier in an amount, basedupon the total weight of the carrier, of from about 1 percent to about90 percent (e.g., from about 5 percent to about 50 percent). Water maybe present in the carrier (prior to use) in an amount, based upon thetotal weight of the carrier, of from about 5 percent to about 95 percent(e.g., from about 50 percent to about 90 percent).

The carrier may also contain: preservatives (such as cresol,chlorocresol, benzyl alcohol, methyl p-hydroxylbenzoate, propylp-hydroxybenzoate, phenol, thimerosal, benzalkonium chloride,benzethonium chloride, and phenylmercuric nitrate); stabilizing agentsor antioxidants (such as ascorbic acid, ascorbic acid esters,butylhydroxy anisole, butylhydroxy toluene, cysteine, N-acetylcysteine,sodium bisulfite, sodium metabisulfite, sodium formaldehydesulfoxylate,acetone sodium bisulfite, tocopherols, and nordihydroguaiaretic acid);chelating agents (such as ethylenediaminetetraacetic acid and itssalts); buffers (such as acetic acid, citric acid, phosphoric acid,glutamic acid, and salts thereof); and tonicity adjusting agents (suchas sodium chloride, sodium sulfate, dextrose and glycerin).

In one embodiment, the carrier may also contain a suspending materialand/or a fluid-absorbing material (e.g., for physically stabilizing theingredients of the carrier). Examples of suspending materials include,but are not limited to: cotton-based gauze; non-woven pads made of rayonor a mixture of rayon, polyester and/or other polymer fibers; open-cellfoam and sponge-like materials contained of polyurethane, polyesterand/or other polymers; and cross-linked and non-cross-linked gellingmaterials, such as polyacrylamide, polyvinyl alcohol, gelatin,hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose,methylcellulose, and carboxymethylcellulose.

Examples of fluid-absorbing material include, but are not limited to:cross-linked and non-cross-linked polymers; swellable polymers such aswater-swollen cellulose derivatives (e.g., methylcellulose (MC),hydroxyethyl methylcellulose (HEMA), hydroxypropyl methylkcellulose(HPMC), ethylhydroxyethyl cellulose (EHEC), hydroxyethylcellulose (HEC),hydroxypropylcellulose (HPC), and carboxymethlcellulose (CMC) and theirsalts); polyvinyl alcohol (PVA); polyvinylpyrrolidone (PVP);polyethylene oxide (PEO); polymers prepared by monomers such ashydroxyethyl methacrylate (HEMA), hydroxyethoxyethyl emthacrylate(HEEMA), hydroxydiethoxyethl methacrylate (HDEEMA), methyoxyethylmethacrylate (MEMA), methoxyethoxyethyl methacrylate (MEEMA),methyldiethoxyethyl methacrylate (MDEEMA), ethylene glycoldimethacrylate (EGDMA), n-vinyl-2pyrrolidone (NVP), methacrylic acid(MA), and vinyl acetate (VAC); polycrylamide; gelatin; gums andpolysaccharides such as gum arabic, gum karaya, gum tragacanth, guargum, gum benzoin, and alginic acid and their salts; polyethylene glycol(PEG); polypropylene glycol (PPG); and clays or other swellable mineralssuch as bentonite and montmorillonite. The amount of fluid absorbablematerial in the carrier may range from about 0.1% to about 95%, byweight, such as from about 1% to about 20%, by weight, of the carrier.

Another embodiment of the present invention is directed to pairing oneor more inert conductive electrodes in order to electrochemicallygenerate oxidizing or reducing agents from electrochemically reactivematerials in situ in the carrier. Such oxidizing or reducing agents canbe used as active agents to treat barrier membrane conditions.

Examples of the electrochemically reactive materials in the carrieraccording to the present invention include, but are not limited to,water and compounds containing the elements selected from the PeriodicTable of the Elements VIB and VIIB (such as oxygen, sulfur, fluorine,chlorine, bromine, and iodine).

In one embodiment, the reactive material reacts with the inert anode toform an oxidizing agent. Examples of such a reactive material includes,but is not limited to, the ions OH , Cl⁻, I⁻, Br⁻, SO₃ ²⁻, and HCO₃ ⁻.The present device, thus, enables to generation of oxidizing agents,such as nascent oxygen (e.g., singlet oxygen), chlorine and chlorinedioxide gases, which are difficult to formulate in a conventionaltopical product.

In one embodiment, the reactive material reacts with the inert cathodeto form reducing agent. Examples of such a reactive material includes,but is not limited to, oxidized or disulfide forms of thio-compoundswith one or more sulfhydryl functional groups, thio-containing aminoacids and their salts or esters, and sulfides. Examples of suchthio-compounds include, but are not limited to: thioglycolic acid andits salts, such as thioglycolates of calcium, sodium, strontium,potassium, ammonium, lithium, magnesium, and other metal salts;thioethylene glycol; thioglycerol; thioethanol; thioactic acid; andthiosalicylic acid; and their salts. Examples of the thio-containingamino acids include, but are not limited to, L-cysteine, D-cysteine,DL-cysteine, N-acetyl-L-cysteine, DL-homocysteine, L-cysteine methylester, L-cysteine ethyl ester, N-carbamoyl cysteine, glutathione, andcysteamine. Examples of sulfides, include but are not limited to,calcium, sodium, potassium, lithium and strontium sulfides andglutathione disulfide. The inert cathode converts the aforementionedreactive oxidized or disulfide form of a sulfur-containing compound to athio-containing compound, or a sulfydryl-containing compound. Examplesof such a conversion is the conversion of cystine to cysteine and theconversion of the oxidized form of glutathione to glutathione.

In one embodiment, the concentration of the reactive material in thecarrier may range from about 0.01% to about 25%, by weight, such as fromabout 0.1% to about 10%, by weight, of the carrier. The pH value of thecarrier may range from about pH 1.5 to about pH 9, preferably from pH 2to pH 7, and most preferably from about pH 3 to pH 5.

In one embodiment, the carrier contains an adhesive. The adhesive isused to affix the device to the barrier membrane. Examples ofhydrophobic adhesives include, but are not limited to, silicones,polyisobutylenes and derivatives thereof, acrylics, natural rubbers, andcombinations thereof. Examples of silicone adhesives include, but arenot limited to, Dow Corning 355 available from Dow Corning of Midland,Mich.; Dow Corningo X7-2920; Dow Corning X7-2960; and GE 6574 availablefrom General Electric Company of Waterford, N.Y. Examples of acrylicadhesives include, but are not limited to, vinyl (D acetate-acrylate)multipolymers such as Gelva 7371, available from Monsanto Company of St.Louis, Mo.; Gelvao 7881; Gelva 2943; and 1-780 medical grade adhesiveavailable from Avery Dennison of Painesville, Ohio. Examples ofhydrophilic adhesives include, but are not limited to, gum papaya andother natural gums, MC, HEMA, HPMC, EHEC, HEC, HPC, CMC, PAV, PVP, PEO,HEMA, HEEMA, HDEEMA, MEMA, MEEMA, MDEEMA, EGDMA, NVP MA, VAC,polycrylamide. getatins, gum arabic, gum karaya, gum tragacanth, guargum, gum benzoin, and alginic acid and their salts, polyethylene glycol(PEG), and polypropylene glycol (PPG).

In one embodiment, the concentration of the adhesive in the carrier mayrange from about 0.1% to about 95%, by weight, such as from about 1% toabout 20%, by weight, of the carrier.

Electrodes

The conductive electrodes of the present invention may be a reactiveconductive electrodes or inert conductive electrodes. What is meant by a“reactive conductive electrode” is that the conductive electrode itselfgoes through a change in its chemical composition during the electrodechemical reactions occurring with the electric current passing throughthe electrode during the process. In one embodiment, the reactiveconductive electrode is made of reactive materials such as metal halides(e.g., silver-silver chloride (Ag/AgCl), silver-silver bromide, andsilver-silver iodide). In this case, the primary electrochemicalreaction at the cathode surface is conversion of solid silver halide tometallic silver with little unwanted consumption of the oxidizing agentsgenerated by the anode. The released halide ions may be subsequentlyoxidized to oxidizing agents, such as chloride ions to chlorine (Cl₂),hypochlorous acid (HClO), and hypochlorite ions (ClO⁻), and iodide ionsto iodine.

What is meant by an “inert conductive electrode” is that the conductiveelectrode itself does not go through a change in its chemicalcomposition. In one embodiment, the anode is made of an inert conductiveelectrode, so that the electrochemical process at the surface of theanode generates oxidizing agents such as nascent oxygen (e.g., byelectrolysis of water) and/or chlorine-containing oxidizing agents suchas chlorine, hypochlorite, chlorate and perchlorate, and chlorinedioxide. Nascent oxygen is an oxidizing agent that is inhibitive to P.acnes, and chlorine-containing oxidizing agents are potent antimicrobialagent with bacteriacidal activity.

In one embodiment, the inert conductive electrode is made of, or coatedon the surface with, an inert materials such as noble metals (e.g.,gold, platinum, or gold-coated conductive metals), conductive carbon(e.g., glassy carbon or graphite), carbon-embedded polymers (e.g.,carbon silicone rubbers), conductive carbon polymer foam or sponge,silver halide-coated silver (e.g., silver chloride-coated silver, silverbromide-coated silver, and silver iodide-coated silver), and corrosiveresistant alloys.

Active Agents

In one embodiment, the carrier contains one or more active agents. Whatis meant by an “active agent” is a compound (e.g., a synthetic compoundor a compound isolated from a natural source) that has a cosmetic ortherapeutic effect on the barrier membrane.

In one embodiment, the carrier contains an anti-acne and/or anti-rosaceaagent. Examples of anti-acne and anti-rosacea agents include, but arenot limited to: retinoids such as tretinoin, isotretinoin, motretinide,adapalene, tazarotene, azelaic acid, and retinol; salicylic acid;benzoyl peroxide; resorcinol; sulfur; sulfacetamide; urea; antibioticssuch as tetracycline, metronidazole, and erythromycin; anti-inflammatoryagents such as corticosteroids (e.g., hydrocortisone), ibuprofen,naproxen, and hetprofen; and imidazoles such as ketoconazole andelubiol; and salts, esters, and other derivatives thereof. Otherexamples of anti-acne active agents include essential oils,alpha-bisabolol, dipotassium glycyrrhizinate, camphor, □-glucan,allantoin, feverfew, flavonoids such as soy isoflavones, saw palmetto,chelating agents such as EDTA, lipase inhibitors such as silver andcopper ions, hydrolyzed vegetable proteins, inorganic ions of chloride,iodide, fluoride, and their nonionic derivatives chlorine, iodine,fluorine, and other valences, synthetic phospholipids and naturalphospholipids such as Arlasilk™ phospholipids CDM, SV, EFA, PLN, and GLA(Uniqema, ICI Group of Companies, Wilton, UK).

In one embodiment, the device of the present invention contains ananti-aging agent. Examples of suitable anti-aging agents include, butare not limited to: inorganic sunscreens such as titanium dioxide andzinc oxide; organic sunscreens such as octyl-methoxy cinnamates;retinoids; vitamins such as vitamin E, vitamin A, vitamin C, and vitaminB and vitamin salts or derivatives such as ascorbic acid di-glucosideand vitamin E acetate or palmitate; alpha hydroxy acids such as glycolicacid, citric acid, lactic acid, malic acid, mandelic acid, ascorbicacid, alpha-hydroxybutyric acid, alpha-hydroxyisobutyric acid,alpha-hydroxyisocaproic acid, atrrolactic acid, alpha-hydroxyisovalericacid, ethyl pyruvate, galacturonic acid, glucoheptonic acid,glucoheptono 1,4-lactone, gluconic acid, gluconolactone, glucuronicacid, glucuronolactone, isopropyl pyruvate, methyl pyruvate, mucic acid,pyruvic acid, saccharic acid, saccaric acid 1,4-lactone, tartaric acid,and tartronic acid; beta hydroxy acids such as beta-hydroxybutyric acid,beta-phenyl-lactic acid, and beta-phenylpyruvic acid; and botanicalextracts such as green tea, soy, milk thistle, algae, aloe, angelica,bitter orange, coffee, goldthread, grapefruit, hoellen, honeysuckle,Job's tears, lithospermum, mulberry, peony, puerarua, nice, andsafflower; and salts, esters, and other derivatives thereof.

In one embodiment, the carrier contains a depigmentation agent. Examplesof suitable depigmentation agents include, but are not limited to: soyextract; soy isoflavones; retinoids such as retinol; kojic acid; kojicdipalmitate; hydroquinone; arbutin; transexamic acid; vitamins such asniacin and vitamin C; azelaic acid; linolenic acid and linoleic acid;placertia; licorice; and extracts such as chamomile and green tea; andsalts, esters, and other derivatives thereof.

In one embodiment, the carrier contains a plant extract. Examples ofplant extracts include, but are not limited to, feverfew, soy, glycinesoja, oatmeal, what, aloe vera, cranberry, hazel witch, alnus, arnica,artemisia capillaris, asiasarum root, birrh, calendula, chamomile,cnidium, comfrey, fennel, galla rhois, hawthorn, houttuynia, hypericum,jujube, kiwi, licorice, magnolia, olive, peppermint, philodendron,salvia, sasa albo-marginata, natural or synthetic isoflavonoids, soyisoflavones, natural or synthetic essential oils.

In one embodiment, the carrier contains metals such as metal ions orfine powders. Examples of such metals include, but are not limited to,gold, silver, copper, zinc.

Other active agents include those commonly used as for topical treatmentand in cosmetic treatment of skin tissues, such as topical antibioticsfor wounds, topical antifungal drugs to treat fungal infections of theskin and nails, and antipsoriatic drugs to treat psoriatic lesions ofthe skin and psoriatic nails.

Examples of antifungal drugs include but are not limited to miconazole,econazole, ketoconazole, sertaconazole, itraconazole, fluconazole,voriconazole, clioquinol, bifoconazole, terconazole, butoconazole,tioconazole, oxiconazole, sulconazole, saperconazole, clotrimazole,undecylenic acid, haloprogin, butenafine, tolnaftate, nystatin,ciclopirox olamine, terbinafine, amorolfine, naftifine, elubiol,griseofulvin, and their pharmaceutically acceptable salts. In oneembodiment, the antifungal drugs are an azole, an allylamine, or amixture thereof.

Examples of antibiotics (or antiseptics) include but are not limited tomupirocin, neomycin sulfate bacitracin, polymyxin B, 1-ofloxacin,tetracyclines (chlortetracycline hydrochloride, oxytetracycline-10hydrochloride and tetrachcycline hydrochoride), clindamycin phsphate,gentamicin sulfate, metronidazole, hexylresorcinol, methylbenzethoniumchloride, phenol, quaternary ammonium compounds, tea tree oil, and theirpharmaceutically acceptable salts.

Examples of antimicrobials include but are not limited to salts ofchlorhexidine, such as lodopropynyl butylcarbamate, diazolidinyl urea,chlorhexidene digluconate, chlorhexidene acetate, chlorhexideneisethionate, and chlorhexidene hydrochloride. Other cationicantimicrobials may also be used, such as benzalkonium chloride,benzethonium chloride, triclocarbon, polyhexamethylene biguanide,cetylpyridium chloride, methyl and benzothonium chloride. Otherantimicrobials include, but are not limited to: halogenated phenoliccompounds, such as 2,4,4′,-trichloro-2-hydroxy diphenyl ether(Triclosan); parachlorometa xylenol (PCMX); and short chain alcohols,such as ethanol, propanol, and the like. In one embodiment, the alcoholis preferably at a low concentration (e.g., less than about 10% byweight of the carrier, such as less than 5% by weight of the carrier) sothat it does not cause undue drying of the barrier membrane.

Examples of antipsoriatic drugs or drugs for seborrheic dermatitistreatment include, but are not limited to, corticosteroids (e.g.,betamethasone dipropionate, betamethasone valerate, clobetasolpropionate, diflorasone diacetate, halobetasol propionate,triamcinonide, dexamethasone, fluocinonide, fluocinolone acetonide,halcinonide, triamcinolone acetate, hydrocortisone, hydrocortisonevenerate, hydrocortisone butyrate, aclometasone dipropionte,flurandrenolide, mometasone furoate, methylprednisolone acetate),methotrexate, cyclosporine, calcipotriene, anthraline, shale oil andderivatives thereof, elubiol, ketoconazole, coal tar, salicylic acid,zinc pyrithione, selenium sulfide, hydrocortisone, sulfur, menthol, andpramoxine hydrochloride, and salts, esters, and other derivativesthereof. Examples of anti-viral agent, include, but are not limited to,imiquimod and its derivatives, podofilox, podophyllin, interferon alpha,acyclovir, famcyclovir, valcyclovir, reticulos and cidofovir.

Examples of anti-inflammatory agent, include, but are not limited to,suitable steroidal anti-inflammatory agents such as corticosteroids suchas hydrocortisone, hydroxyltriamcinolone alphamethyl dexamethasone,dexamethasone-phosphate, beclomethasone dipropionate, clobetasolvalerate, desonide, desoxymethasone, desoxycorticosterone acetate,dexamethasone, dichlorisone, diflorasone diacetate, diflucortolonevalerate, fluadrenolone, fluclarolone acetonide, fludrocortisone,flumethasone pivalate, fluosinolone acetonide, fluocinonide, flucortinebutylester, fluocortolone, fluprednidene (fluprednylidene)acetate,flurandrenolone, halcinonide, hydrocortisone acetate, hydrocortisonebutyrate, methylprednisolone, triamcinolone acetonide, cortisone,cortodoxone, flucetonide, fludrocortisone, difluorosone diacetate,fluradrenalone acetonide, medrysone, amciafel, amcinafide, betamethasoneand the balance of its esters, chlorprednisone, chlorprednisone acetate,clocortelone, clescinolone, dichlorisone, difluprednate, flucloronide,flunisolide, fluoromethalone, fluperolone, fluprednisolone,hydrocortisone valerate, hydrocortisone cyclopentylproprionate,hydrocortamate, meprednisone, paramethasone, prednisolone, prednisone,beclomethasone dipropionate, betamethasone dipropionate, andtriamcinolone. The preferred steroidal anti-inflammatory for use in thepresent invention is hydrocortisone. A second class of anti-inflammatoryagents which is useful in the compositions of the present inventionincludes the nonsteroidal anti-inflammatory agents.

Other active agents include, but are not limited to, wound healingenhancing agent, scar reducing agents, analgesic agents, anesthetics,hair growth enhancing agents such as minoxadil, antihypertensives, drugsto treat coronary artery diseases, anticancer agents, endocrine andmetabolic medication, neurologic medications, medication for cessationof chemical additions, motion sickness, and protein and peptide drugs.

The amount of the active agent in the carrier will depend on the activeagent and/or the intended use of the device. In one embodiment, thecarrier contains a safe and effective amount of the active agent, forexample, from about 0.001 percent to about 20 percent, by weight, suchas from about 0.01 percent to about 5 percent, by weight, of thecarrier.

Light Emitting Diode

In one embodiment, the device contains one or more light emittingdiodes. Light emitting diodes (LEDs) of certain spectrum may beincorporated into the device to emit light to the barrier membrane(e.g., to treat skin conditions such as acne and rosacea). The lightemitting diode may also provide a signal to the user indicating that thedevice is operating properly.

The spectrum of the LED's according to the current invention may rangefrom about 300 nm to about 1500 nm, such as from about 350 nm to about1000 nm. In one embodiment, the range of the LED includes violet-blue,green, red, and infrared ranges, e.g., from about 400 nm to about 450 nmsuch as from about 407 nm to about 420 nm; from about 510 nm to about550 nm; from about 600 nm to about 700 nm; and from about 1300 nm toabout 1500 nm. In one embodiment, the device contains two LEDs, one thatemits light having a wavelength of from about 400 nm to about 500 nm andone which emits light from about 700 nm to about 1000 nm.

Photosensitizer agents, such as 5-aminolaevulinic acid (ALA), hypericin,St. John's wort powder or extract, or other synthetic or naturalphotosensitizer agents, may be incorporated into the carrier as activeagents to be delivered and irradiated by the device with LED's of thepresent invention. The light irradiation from the LED's, together withthe photosensitizer agent(s) and other aforementioned active agents,electrochemically generated oxidizing agents (e.g., peroxides, nascentoxygen, chlorine dioxide, and chlorine), and/or electric stimulation ofthe barrier membrane may work synergistically to achieve an improvedefficacy in treating membrane disorders such as acne and rosacea.

Use

In one embodiment, the device is used for the treatment of a barriermembrane condition (e.g., the delivery of an active agent, light, and/orelectricity into the membrane such as the skin, vaginal, or rectalmucosa barrier membrane of a human). In one embodiment, the device isused for the treatment of skin conditions. Examples of such treatmentsinclude, but are not limited to: treatment of acne, rosacea, or othermicrobial infections of the skin; reduction the visible signs of skinaging (e.g., wrinkles, sagging, and age-spots); folliculitis andpseudo-folliculitis barbae; treatment of wounds and lesions (e.g.,enhancing healing and scar reduction); sebum regulations (e.g., sebumreduction or oily/shining skin appearance inhibition or control);pigmentation regulation (e.g., reduction of hyperpigmentation orpigmentation of light skin); hair growth retardation (e.g., skin on theleg) or hair stimulation (e.g., scalp); and treatment of dermatitis(e.g., atopic, contact, or seborrheic dermatitis) and/or psoriasis.

In another embodiment, the device is used for the treatment of mucosalconditions. Examples of such treatments include, but are not limited to:treatment of vaginal candidiasis and vaginosis, genital herpes, andother microbial infections of the mucosa.

Another embodiment of the present invention is the device inducescertain desirable biological responses that facilitate the treatment ofthe barrier membrane conditions. These desirable biological responsesmay be induced by the electric current passage through the barriermembrane, and/or the electrochemically generated oxidizing materials,together with the active agents delivered by iontophoresis from thecarrier, in treating the barrier conditions. Examples of the desirableresponses of the barrier membrane may include, but are not limited to,sebum regulation (e.g., reduction of sebaceous gland activity),inhibition of anaerobotic microbial growth and establishment of ahealthier membrane microflora or (e.g, reduction of P. acne growth andof production of irritating fatty acids), blood vasoconstriction (thuspromoting local accumulation of active agents or removal of dark circleunder the eye due to deoxyhemoglobins), enhanced tissue immunologicalactivity (e.g, increased elimination of pathogenic microbes on tissue'sown defense systems), improved tissue repairing (e.g., enhanced healingand reduced scarring of lesions such as acne lesions), and improvedkeratolytic activity of the carrier (e.g., softening of keratin plugs ofcomedos in whiteheads and blackheads of acne, and facilitating theirremoval).

In another aspect, the invention also features the method of convertingan active agent from a less active form to a more active form viaoxidation or reduction via an inert electrode (e.g., cystine tocysteine, disulfide acetyl-cysteine to acetyl-cysteine, and retinol toretinoic acid). Thus, an unstable agent can be stored in a more stableform and converted to its active form prior to administration. In afurther aspect, the generation of reducing agents by the device of thepresent invention can be used to stabilize oxygen-labile active agents.Examples of such oxygen-labile active agents include, but are notlimited to, retinoids, ascorbic acid, and benzoyl peroxide.

Shape

The device may be fabricated into various shapes and sizes to fit thecontours of various anatomical surfaces of the barrier membranes. Forexamples, it may be made as a whole facial mask with openings/holes toexpose the eyes, eye bows, nose, and mouth; a partial facial maskcovering only the upper or lower half of the face; or a patch coveringonly the forehead, or the under eye region, the chin and jaw region, theneck, the back, wound, acne lesion or pimple, or other specific area ofa barrier membrane in need of treatment.

Devices

One embodiment of the present invention is represented schematically inFIG. 1. The device 500 contains a removable release liner 100, a carrierlayer 120, a first conductive electrode 140, a second conductiveelectrode 240, electric lead wires 110 and 210 connecting the two polesof a battery 320 to the two oppositely charged conductive electrodes, anelectric power switch 330 located on the lead wire 220, a light emittingdiode (LED) 122, a backing layer 160 separating the carrier layer 120from the battery 320, and a battery cover layer 340.

The gap “b” depicts the distance between two conductive electrodes 140and 240 to the release liner (or the membrane following application ofthe device), and the gap “a” represents the distance between twooppositely charged conductive electrodes. In one embodiment, the ratioof gap “a” to gap “b” is at least about 1, such as at least about 2 orat least about 5.

The backing layer 160 may be impermeable to the active agent containedwithin the carrier layer 120, and is preferably not permeable to wateror other solvents in the carrier layer 120. The battery 320 may beencased in an electric insulating, water-impermeable polymer layer (notshown in the figure). The backing layer 160 and the batter cover layer340 may be made of flexible material that is impermeable to water, e.g.,polymers such as polyethylene, polypropylene, polyvinyl acetate,polyurethane, silicone rubber, or polyvinyl chloride.

Optionally, there can be an electric circuit (not shown) in device 500to provide a constant current located between the battery 320 andconductive electrode 140 and/or conductive electrode 240.

In a further embodiment, the backing layer 160 is permeable toelectrochemically generated gases (e.g., oxygen, chlorine, and hydrogen)in order to limit excess accumulation of the gases in the carrier whichcan cause tissue irritation and/or undesirable deformation of thedevice.

The carrier layer 120 is an adhesive hydrogel containing the activeagent. The active agent may be incorporated into the carrier layer 120as dissolved molecules and ions, dispersed solid particles, or liquiddroplets such as cream, lotion, emulsion, multi-emulsion, microemulsion,and/or liposome compositions. The carrier layer 120 may also contain asolid supporting matrix (e.g., a gauze, non-woven or sponge-likematerial).

A removable liner sheet 100 covers the carrier layer 120. The selectionof the removable release-liner 100 is dependent on the type of theadhesive hydrogel used in carrier layer 120. The release liner sheet 100is typically a polymer sheet or a paper or fabric coated with a polymer,which has weak adhesion toward the adhesive hydrogel layer 120, therebyallowing it to be easily removed from the carrier layer 120 prior to usewithout damaging the carrier layer 120. Examples of the polymerstypically used for the release liner 100 are silicones andpolyethylenes. Alternatively, a wax may be used in the place of thepolymer to coat the release liner 100.

In addition to, or in lieu of, the use of an adhesive in the carrierlayer 120, the device 500 may be fastened to the barrier membrane withan adhesive tape, an elastic band, a band with a buckle (similar to aleather watch band), or a Velcro® band.

In order to use device 500, the removable release liner sheet 100 ispeeled off, and the carrier hydrogel layer 120 of the device 500 isaffixed to a barrier membrane, such as the skin, vaginal, or rectalmucosa barrier membrane, of the user. The device may be directly affixedto the barrier membrane if the carrier layer 120 contains an adhesivehydrogel. An electric potential is applied across the conductiveelectrodes 140 and 240 by switching on the power switch 330. Anotherembodiment of the present invention is represented schematically in FIG.2. The battery 320 is located within the carrier layer 120. Theadvantage of this battery arrangement includes reduced bulkiness,enhanced esthetics and user comfort.

Another embodiment of the present invention is represented schematicallyin FIG. 3. Housing 170 contains an adhesive layer 130 coated onto therim of the housing 170 for affixing device 500 to membrane duringapplication. The housing 170 may be made of the same materials as thebacking layer 160 described above. The adhesive in the adhesive layer130 may be a polymeric, pressure sensitive and/or nonconductive.Suitable adhesive materials include, but are not limited to, silicones,polyisobutylenes and derivatives thereof, acrylics, natural rubbers, andcombinations thereof. Suitable silicone adhesives include, but are notlimited to, Dow Corning 355 (available from Dow Corning of Midland,Mich.); Dow Corning X7-2920; Dow Corning 0 X7-2960; GE 6574 (availablefrom General Electric Company of Waterford, N.Y.); and silicone pressuresensitive adhesives. Suitable acrylic adhesives include, but are notlimited to, vinyl acetate-acrylate multipolymers, including, such asGelva-7371 (available from Monsanto Company of St. Louis, Mo.); Gelva T7881; Gelvac 2943; 1-780 medical grade adhesive available from AveryDennison of Painesville, Ohio; and acrylic pressure sensitive adhesives.

When a zinc air battery is used as the power source of the device 500,the battery 320 is constructed in such a way that the orifice on thestainless steel cover is facing the opposite side of the carrier layer120. An orifice is made on the battery cover layer to expose the orificeon the zinc air battery that is covered by a removableoxygen-impermeable cover. In this case, the power switch 230 is replacedby the removable oxygen-impermeable cover. The removableoxygen-impermeable cover can be used to begin (by removing it) or tohalt the electrotransport process of the device (by re-covering theorifice).

In one embodiment, the carrier layer 120 contains at least two activeagents carrying opposite electric charges. One example of such acomposition is a composition containing from about 0.5 to about 2%salicylic acid and from about 0.01 to about 0.2% of a cationicquaternary ammonium antimicrobial agents (such as benzalkonium chloride,benzethonium chloride, methyl benzethonium chloride, and cetylpyridiniumchloride), phenol, and/or chlorhexidine gluconate. The device 500 of thepresent invention can simultaneously deliver both active agents ofopposite charges into the membrane.

The backing layer 160 may have some gas permeability, so called“breathable backing”. The examples of such “breathable backing” materialinclude, but are not limited to, a cotton or synthetic woven andnonwoven fabric layer, such as those fabric materials commonly used forbandages and sports bandages.

The lighting portion of the LED 122 is preferable located in the carrierlayer 120 in close proximity to the skin. Locating the light source inthe carrier layer 120 affixed to the barrier membrane has an advantageof minimizing the loss of light energy from reflection of skin surface.In addition, a light reflective layer may be used as the backing layer160 (e.g., metalized polymer film) to further enhance the efficacy ofphototherapy, and to achieve more homogeneous irradiation. The backinglayer 160 may optionally be perforated as certain spots to make thelight visible to the user to serve as an indicator that the device isworking normally.

FIGS 4 and 5 disclose one embodiment of the two different configurationsof conductive electrode 140 and 240 in carrier layer 120.

Another embodiment of the present invention is represented schematicallyin FIG. 6. The electrotransport device 800 contains two electrodeassemblies 200 and 600, respective adhesive layers 230 and 630,respective carrier layers 220 and 620, respective conductive electrodes240 and 640, respective light emitting diodes 222 and 622, respectivehousings 270 and 670, respective electric leads 210 and 610, battery 320and electric switch 330. Similar to the aforementioned typicaliontophoresis device, the two electrode assemblies 200 and 600 are to beaffixed to the barrier membrane with an electric insulation betweenthem, after the release liner 100 is removed prior to use.

EXAMPLES

Examples of several carriers, including the weight percentage range ofthe ingredients of such carriers, are set forth in Table 1.

TABLE 1 Percent by Weight of the Carrier Component No. 1 No. 2 No. 3 No.4 No. 5 No. 6 Salicylic acid 0.1-10   2 2 0 0 0.1-10   Benzyl peroxide 00 0 0.5-10   0 0 Sulfur 0 0 0 0 3 3 Resorcinol 0 0 0 1 1 1 Benzalkoniumchloride 0-2    0.1   0.1 0-2  0-2  0-2  Benzethonium or 0-2  0 0 0-2 0-2  0-2  methylbezethonium chloride Cetylpyridium chloride 0-2    0.1  0.1 0-2  0-2  0-2  Phospholipid CDM 0-40 5 5 0-40 0-40 0-40 Hydrogenperoxide 0-30 0 3 0-30 0-30 0-30 Buffer (citrate, 0-10 2 2 0-10 0-100-10 lactate, or phosphate salts of sodium, potassium, or lithiumGelling agent 0-20 5 5 0-20 0-20 0-20 (e.g., polyacrylates, cellulose,natural or synthetic gums, or polyacrylamide) Chelating agent 0-2    0.1  0.1 0-2  0-2  0-2  (e.g., EDTA) Propylene glycol 0-30 20  15  0-300-30 0-30 Polyethylene 0-50 0 0 0-50 0-50 0-50 glycol Polypropylene 0-400 0 0-40 0-40 0-40 glycol Ethyl alcohol 0-50 0 15  0-50 0-50 0-50Isopropyl alcohol 0-50 0 0 0-50 0-50 0-50 Dimethyl 0-20 2 0 0-20 0-200-20 isosorbide Isopropyl 0-30 1 1 0-30 0-30 0-30 myristate Purifiedwater Qs to Qs to Qs to Qs to Qs Qs to 100 100 100 100 to 100 100

It is understood that while the invention has been described inconjunction with the detailed description thereof, that the foregoingdescription is intended to illustrate and not limit the scope of theinvention, which is defined by the scope of the appended claims. Otheraspects, advantages, and modifications are within the claims.

1. A method of treating a skin condition in skin, said method comprisingapplying to said skin a device having a barrier membrane contactingsurface that administers an oxidizing agent to said skin, wherein saiddevice comprises: a power source; a first conductive electrode, whereinsaid first conductive electrode is an inert anode; a second conductiveelectrode, wherein said second conductive electrode is a cathode; and acarrier comprising water; wherein said power source is in electriccommunication with said first conductive electrode and said secondconductive electrode, wherein said first conductive electrode is inionic communication with said carrier, wherein said oxidizing agent isgenerated by electric current passing from the first conductiveelectrode through said carrier, wherein said carrier is in communicationwith said barrier membrane contacting surface, and wherein said secondconductive electrode is in ionic communication with said carrier andwherein said device is adapted to be affixed to said skin and to deliverelectric current from said first conductive electrode, through saidcarrier, through said skin, and through said carrier to said secondconductive electrode.
 2. A method of claim 1, wherein said secondconductive electrode is a reactive electrode.
 3. A method of claim 2,said oxidizing agent is nascent oxygen.
 4. A method of claim 1, whereinsaid oxidizing agent is nascent oxygen.
 5. A method of claim 1, whereinsaid device comprises a housing and wherein said first conductiveelectrode, said second conductive electrode, and said carrier are withinsaid housing.
 6. A method of claim 1, wherein said carrier is asemi-solid.
 7. A method of claim 1, wherein said skin condition is acneor rosacea.
 8. A method of claim 1, wherein said carrier furthercomprises an active agent selected from the group consisting ofsalicylic acid, benzoyl peroxide, resorcinol, a retinoid, and sulfur. 9.A device of claim 1, wherein said power source produces conventionaldirect current and wherein said device is adapted to be affixed to saidskin and to deliver said electric current from said power source andsaid oxidizing agent through said barrier membrane contacting surface tosaid skin.
 10. A method of administering an oxidizing agent to a barriermembrane, said method comprising applying to said membrane a devicehaving a barrier membrane contacting surface that administers saidoxidizing agent to said barrier membrane, wherein said device comprises:a power source; a first conductive electrode, wherein said firstconductive electrode is an inert anode; a second conductive electrode,wherein said second conductive electrode is a cathode; and a carriercomprising water; wherein said power source is in electric communicationwith said first conductive electrode and said second conductiveelectrode, wherein said first conductive electrode is in ioniccommunication with said carrier, wherein said oxidizing agent isgenerated by electric current passing from the first conductiveelectrode through said carrier, and wherein said carrier is incommunication with said barrier membrane contacting surface, and whereinsaid second conductive electrode is in ionic communication with saidcarrier and wherein said device is adapted to be affixed to said barriermembrane and to deliver electric current from said first conductiveelectrode, through said carrier, through said barrier membrane, andthrough said carrier to said second conductive electrode.
 11. A methodof claim 10, wherein said second conductive electrode is a reactiveelectrode.
 12. A method of claim 11, wherein said oxidizing agent isnascent oxygen.
 13. A method of claim 10, wherein said oxidizing agentis nascent oxygen.
 14. A method of claim 10, wherein said devicecomprises a housing and wherein said first conductive electrode, saidsecond conductive electrode, and said carrier are within said housing.15. A method of claim 10, wherein said carrier is a semi-solid.
 16. Amethod of claim 10, wherein said carrier further comprises an activeagent selected from the group consisting of salicylic acid, benzoylperoxide, resorcinol, a retinoid, and sulfur.
 17. A method of claim 10,wherein said active agent is selected from the group consisting of ananti-acne agent, an anti-rosacea agent, an anti-aging agent, adepigmentation agent, an antibiotic agent, an antifungal agent, ananti-psoriatic agent, an antimicrobial agent, an anti-viral agent, andan anti-inflammatory agent.
 18. A method of claim 10, wherein said powersource produces conventional direct current and wherein said devicedelivers said electric current from said power source and said oxidizingagent through said barrier membrane contacting surface to said barriermembrane.